Download Leukaemia Section t(2;5)(p23;q35) SQSTM1/A LK Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
OPEN ACCESS JOURNAL AT INIST-CNRS
Leukaemia Section
Short Communication
t(2;5)(p23;q35) SQSTM1/ALK
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
(JLH)
Published in Atlas Database: November 2011
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t0205p23q35ID1584.html
DOI: 10.4267/2042/47305
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
one glycin-rich region), a transmembrane domain, and
an intracellular region (composed of a tyrosine kinase
domain). Membrane receptor tyrosine kinase.
Germinal mutations
In familial neuroblastoma.
Somatic mutations
Fusion proteins in anaplastic large cell lymphoma,
some diffuse large B-cell lymphomas, inflammatory
myofibroblastic tumours, and some non-small cell lung
cancers. Somatic mutations in sporadic neuroblastoma
(review in Allouche, 2010).
Identity
Note
Not to be confused with the t(2;5)(p23;q35) with
NPM1-ALK involvement.
Clinics and pathology
Disease
ALK-positive large B-cell lymphoma (ALK+ LBCL)
Phenotype/cell stem origin
SQSTM1
One case to date, a 67-year-old male patient (Takeuchi
et al., 2011).
Location
5q35.3
Protein
SQSTM1 (sequestosome1), also called p62, is a
scaffolding protein with several interaction domains; it
is composed of an OPR domain (octicosapeptide repeat
(PB1 dimerization domain)), a Zn finger, a LIM
protein-binding region, a TRAF6-binding motif, a
PEST sequence (proline, glutamic acid, serine, and
threonine rich), a LIR motif (LC3 interaction region,
SGGDDDWTHLSS), a second PEST sequence, a KIR
(keap1 interacting region), and an UBA (ubiquitinassociated) domain. Interacts with Caspase-8 and the
apoptosis, machinery, MAPK kinases such as MAP2K5
(15q23), LCK (1p34), NBR1 (17q21), PRKCI (3q26),
PAWR (12q21), RIPK1 (6p25), TRAF6 (11p12) and
NTRK1 (1q23) and the NF-kappaB pathway, KEAP1
(19p13), GABARAPL1 (12p13), MAP1LC3A/LC3
(20q11), and ubiquitin. Mediates the interaction
between TRAF6 and CYLD (16q12). Implicated in the
activation of the transcription factor NF-kappaB.
Cytology
Anti-ALK immunohistochemistry showed a diffuse
cytoplasmic staining pattern, in contrast with the
nuclear and cytoplasmic pattern usually sen in the
NPM1-ALK fusion gene/protein.
Prognosis
Complete remission was obtained, but the patient
relapsed four months later.
Genes involved and proteins
ALK
Location
2p23
Protein
ALK is composed of an extracellular region
(containing two MAM (meprin, A-5 protein, and
receptor protein-tyrosine phosphatase mu) and one
LDLa (low-density lipoprotein receptor) domains, and
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4)
293
t(2;5)(p23;q35) SQSTM1/ALK
Huret JL
Lamark T, Kirkin V, Dikic I, Johansen T. NBR1 and p62 as
cargo receptors for selective autophagy of ubiquitinated
targets. Cell Cycle. 2009 Jul 1;8(13):1986-90
Involved in the autophagy-lysosome pathway. Plays a
role in the formation of cytoplasmic proteinaceous
inclusions in various pathologic situations where
autophagy is inactivated (Geetha and Wooten, 2002;
Lamark et al., 2009; Moscat and Diaz-Meco, 2009;
Moscat et al., 2009; Ichimura and Komatsu, 2010;
Komatsu and Ichimura, 2010; Moscat and Diaz-Meco,
2011).
Germinal mutations
Mutated in Paget's disease of bone.
Moscat J, Diaz-Meco MT. p62 at the crossroads of autophagy,
apoptosis, and cancer. Cell. 2009 Jun 12;137(6):1001-4
Moscat J, Diaz-Meco MT, Wooten MW. Of the atypical PKCs,
Par-4 and p62: recent understandings of the biology and
pathology of a PB1-dominated complex. Cell Death Differ.
2009 Nov;16(11):1426-37
Allouche M.. ALK (anaplastic lymphoma receptor tyrosine
kinase) Atlas Genet Cytogenet Oncol Haematol. February
2010. URL: http://AtlasGeneticsOncology.org/Genes/ALK.html
Result of the chromosomal
anomaly
Ichimura Y, Komatsu M.. Selective degradation of p62 by
autophagy. Semin Immunopathol. 2010 Dec;32(4):431-6. Epub
2010 Sep 3. (REVIEW)
Komatsu M, Ichimura Y.. Physiological significance of selective
degradation of p62 by autophagy. FEBS Lett. 2010 Apr
2;584(7):1374-8. Epub 2010 Feb 12. (REVIEW)
Hybrid gene
Description
Exon 5 of SQSTM1 fused to the ALK exon 20.
Fusion protein
Moscat J, Diaz-Meco MT.. Feedback on fat: p62-mTORC1autophagy connections. Cell. 2011 Nov 11;147(4):724-7.
(REVIEW)
Description
Fuses the PB1 dimerization domain of SQSTM1 to the
tyrosine kinase domain of ALK, resulting in a
constitutive activation of the ALK kinase domain.
Takeuchi K, Soda M, Togashi Y, Ota Y, Sekiguchi Y, Hatano
S, Asaka R, Noguchi M, Mano H.. Identification of a novel
fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma.
Haematologica. 2011 Mar;96(3):464-7. Epub 2010 Dec 6.
This article should be referenced as such:
References
Huret JL. t(2;5)(p23;q35) SQSTM1/ALK. Atlas
Cytogenet Oncol Haematol. 2012; 16(4):293-294.
Geetha T, Wooten MW. Structure and functional properties of
the ubiquitin binding protein p62. FEBS Lett. 2002 Feb
13;512(1-3):19-24
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(4)
294
Genet